Research Article

A Transcriptional Switch Mediated by Cofactor Methylation

Science  21 Dec 2001:
Vol. 294, Issue 5551, pp. 2507-2511
DOI: 10.1126/science.1065961

You are currently viewing the abstract.

View Full Text

Abstract

We describe a molecular switch based on the controlled methylation of nucleosome and the transcriptional cofactors, the CREB-binding proteins (CBP)/p300. The CBP/p300 methylation site is localized to an arginine residue that is essential for stabilizing the structure of the KIX domain, which mediates CREB recruitment. Methylation of KIX by coactivator-associated arginine methyltransferase 1 (CARM1) blocks CREB activation by disabling the interaction between KIX and the kinase inducible domain (KID) of CREB. Thus, CARM1 functions as a corepressor in cyclic adenosine monophosphate signaling pathway via its methyltransferase activity while acting as a coactivator for nuclear hormones. These results provide strong in vivo and in vitro evidence that histone methylation plays a key role in hormone-induced gene activation and define cofactor methylation as a new regulatory mechanism in hormone signaling.

  • * To whom correspondence should be addressed. E-mail: evans{at}salk.edu

View Full Text

Cited By...